Quantitative proteomic analysis after neuroprotective MyD88 inhibition in the retinal degeneration 10 mouse

Tal Carmy-Bennun, Ciara Myer, Sanjoy K. Bhattacharya, Abigail S. Hackam

Research output: Contribution to journalArticlepeer-review

Abstract

Progressive photoreceptor death occurs in blinding diseases such as retinitis pigmentosa. Myeloid differentiation primary response protein 88 (MyD88) is a central adaptor protein for innate immune system Toll-like receptors (TLR) and induces cytokine secretion during retinal disease. We recently demonstrated that inhibiting MyD88 in mouse models of retinal degeneration led to increased photoreceptor survival, which was associated with altered cytokines and increased neuroprotective microglia. However, the identity of additional molecular changes associated with MyD88 inhibitor-induced neuroprotection is not known. In this study, we used isobaric tags for relative and absolute quantification (iTRAQ) labelling followed by LC-MS/MS for quantitative proteomic analysis on the rd10 mouse model of retinal degeneration to identify protein pathways changed by MyD88 inhibition. Quantitative proteomics using iTRAQ LC-MS/MS is a high-throughput method ideal for providing insight into molecular pathways during disease and experimental treatments. Forty-two proteins were differentially expressed in retinas from mice treated with MyD88 inhibitor compared with control. Notably, increased expression of multiple crystallins and chaperones that respond to cellular stress and have anti-apoptotic properties was identified in the MyD88-inhibited mice. These data suggest that inhibiting MyD88 enhances chaperone-mediated retinal protection pathways. Therefore, this study provides insight into molecular events contributing to photoreceptor protection from modulating inflammation.

Original languageEnglish (US)
Pages (from-to)9533-9542
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number20
DOIs
StatePublished - Oct 2021

Keywords

  • MyD88
  • Toll-like receptors
  • crystallin
  • iTRAQ
  • photoreceptors
  • proteomics
  • retinal degeneration

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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